Table 1. CpG sites that are associated with multiple biomarkers, and previous associations between the CpG locus diseases.
| CpG Name | Gene(s) annotation CpG Gene name |
Disease related gene function | Biomarker | Pathogenic association of biomarker | Estimate b | P |
|---|---|---|---|---|---|---|
| cg00329615 | Immunoglobulin superfamily member 11 (IGSF11) | IGSF11 stimulates cell growth and is frequently up regulated in intestinal gastric cancer [53] | IL-12 | Inflammation, cancer | 3.48 | 3.8x10-8 |
| MIA | Cancer | 3.52 | 1.8x10-8 | |||
| TNFRSF4 | Cancer | 4.16 | 3.1 x10-10 | |||
| cg02664787 | Opioid binding protein/cell adhesion molecule-like (OPCML) | OPCML is involved in ovarian cancer and studies have shown epigenetic inactivation in ovarian tumors [29] | PlGF | Cardiovascular, cancer | -4.87 | 1.5 x10-8 |
| TNF-RI | Cardiovascular, cancer | -4.46 | 5.3 x10-8 | |||
| cg03636183 c | Coagulation factor II (Thrombin) receptor-like 2 (F2RL3) | F2RL3 helps to sustain platelet aggregation during prolonged thrombin exposures [22] and DNA methylation at F2RL3 has been shown to be a strong predictor of mortality [32]. | WFDC2 | Cancer | -3.41 | 3.1 x10-8 |
| IL-12c | Inflammation, cancer | 4.36 | 9.9 x10-10 | |||
| cg04134748 | PR domain containing 16 (PRDM16) | PRDM16 is associated to left ventricular noncompaction and cardiomyopathy [21] | Flt3L | Inflammation, cancer | 3.96 | 5.3 x10-12 |
| SRC | Cardiovascular | -3.77 | 9.1 x10-9 | |||
| cg05304729 | Myeloid cell nuclear differentiation antigen (MNDA) | MNDAis identified as a marker for nodal marginal zone lymphoma [26] | CXCL11 | Inflammation, cancer | -6.51 | 1.1 x10-9 |
| CXCL9 | Inflammation, cancer | -5.36 | 2.5 x10-8 | |||
| cg07839457 a | NLR family, CARD domain containing 5 (NLRC5) | NLRC5 is involved in immune defense [24] | CXCL11 | Inflammation, cancer | -3.26 | 3.5 x10-11 |
| CXCL9 | Inflammation, cancer | -2.84 | 1.2 x10-10 | |||
| IL-12 | Inflammation, cancer | -2.62 | 2.9 x10-8 | |||
| IL-18 | Cardiovascular, inflammation | -2.6 | 7.0 x10-8 | |||
| cg09801824 | DnaJ (Hsp40) homolog, subfamily B, member 12 (DNAJB12), DNA-damage-inducible transcript 4 (DDIT4) | VMP1 is associated with Lp-PLA2 which is associated with increased cardiovascular risk [23]. VMP1 and MIR21 are involved in cancer risk [28]. | CXCL11 | Inflammation, cancer | 9.91 | 3.6 x10-9 |
| CXCL9 | Inflammation, cancer | 9.67 | 1.2 x10-10 | |||
| cg12785694 | Structural maintenance of chromosome 4 (SMC4) Intraflagellar transport 80 (IFT80) | SMC4 is associated with cancer [25]. | CXCL11 | Inflammation, cancer | -4.43 | 6.7 x10-8 |
| IL-12 | Inflammation, cancer | -4.41 | 8.1 x10-9 | |||
| cg12790638 | Hyaluronan and proteoglycan link protein 3 (HAPLN3), Milk fat globule-EGF factor 8 protein (MFGE8) | HAPLN3 and MFGE8 are involved in various cancers [30,31]. | Adrenomedullin | Cardiovascular, cancer | 3.95 | 7.2 x10-8 |
| Cystatin B | Cardiovascular, cancer | 3.7 | 1.5 x10-8 | |||
| VEGF-A | Cardiovascular, cancer, inflammation | 3.98 | 5.4 x10-8 | |||
| cg16936953a | Vacuole membrane protein 1 (VMP1), Micro-RNA 21 (MIR21) | VMP1 is associated with Lp-PLA2 which is associated with increased cardiovascular risk [23]. VMP1 and MIR21 are involved in cancer risk [28]. | CXCL13 | Cancer | -3.68 | 5.6 x10-9 |
| Follistatin | Cardiovascular, cancer | -3.55 | 1.0 x10-7 | |||
| GDF-15 | Cardiovascular, cancer | -3.74 | 2.5 x10-15 | |||
| IL27-A | Cardiovascular | -3.04 | 8.9 x10-9 | |||
| cg20497205 | Opsin 5 (OPN5) | CX3CL1 | Cardiovascular, inflammation | 9.04 | 4.1 x10-8 | |
| HB-EGF | Cardiovascular, cancer | 8.19 | 4.1 x10-8 |
a. The NLRC5 and VMP1/MIR21 regions consist of multiple associated CpG sites. However, these CpG sites are not independent and therefore only the most significant CpG site is included in this table.
b. The estimates represent change in biomarker values (in standard deviations) per 100% change in DNA methylation level (from 0 to 100%)